Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

How Grapefruit Affects Prescription Drugs

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Does grapefruit in particular help people lose weight?

If someone eats half of a grapefruit three times a day before each meal for a couple months, they may lose about two pounds -- but that's no more than if they ate three apples or pears a day. In one study, the grapefruit eaters not only saw their weight go down, but their waist got slimmer, and their body fat melted away. If, however, we repeat the experiment and instead ask people to drink a half cup of water before each meal, we get the same result. So this belief that grapefruit has some special fat-burning quality appears to be just a long-held myth.

The researchers reported that grapefruit consumers had a drop in weight, a significant drop in cholesterol, and a significant drop in blood pressure. They concluded that consumption of grapefruit daily for six weeks does not significantly decrease body weight, cholesterol, or blood pressure, though. That made me do a little double take, but again, it's because the grapefruit didn't do any better than placebo.

Other studies have found a legitimate cholesterol-lowering benefit of grapefruit, and even a little dip in triglycerides, especially eating red as opposed to white . For example, one study showed a decrease in cholesterol, but only from one life-threatening cholesterol level to another life-threatening cholesterol level. To prevent heart disease, we really have to get down to a total cholesterol of around 150, which is the average cholesterol of those eating diets composed exclusively of plant foods, not just grapefruits (See, for example, One in a Thousand: Ending the Heart Disease Epidemic).

Even though grapefruits alone don't do much, the researchers suggest that people might be more likely to stick with them than cholesterol lowering drugs, noting that most people with heart disease stop taking their statin drugs within a couple years because of the adverse side effects (see Statin Muscle Toxicity). While grapefruits alone don't have any side effects, ironically, combining grapefruits and drugs can make drug side effects even worse.

If we eat lots of fruits and vegetables, we hopefully won't need a lot of drugs (Say No to Drugs by Saying Yes to More Plants), but certain phytochemicals in plants can affect the metabolism of drugs in the body. Grapefruit is the poster child, described as a "pharmacologist's nightmare." Natural phytochemicals in grapefruit suppress the enzymes that help clear more than half of commonly prescribed drugs, and less drug clearance means higher drug levels in the body. This may actually be good if we want a better caffeine buzz from our morning coffee, or our doctors want to help us save thousands of dollars by boosting the effects of expensive drugs instead of just peeing them away.

But higher drug levels may mean higher risk of side effects. Women taking the Pill are normally at a higher risk of blood clots, but even more so, perhaps, if they have been consuming grapefruit. Taking the Pill with grapefruit juice may increase blood drug concentrations by 137 percent.

If suppressing our drug clearance enzymes with grapefruit juice elevates levels of ingested estrogen, what might it be doing to our own estrogen levels? A study associating grapefruit consumption with breast cancer freaked out the medical community, but subsequent studies on even larger groups of women found no evidence of a link. The Harvard Nurses' Study even found a decreased risk of the scariest breast cancer type, so it doesn't look like we have to worry about grapefruit affecting our natural chemistry.

For those prescribed unnatural chemistries, it may be a good idea to discontinue grapefruit consumption for 72 hours before use of a drug that may interact with it. If you don't want to give up your grapefruit, you can ask your doctor about switching from a grapefruit-affected drug like Lipitor to one of the citrus-proof alternatives (the replacement drug chart can be seen in my video, Tell Your Doctor If You Eat Grapefruit).

Other videos on citrus include:

And another video on the risks associated with taking estrogens: Plant-Based Bioidentical Hormones.

Can't eat grapefruit without sprinkling sugar on top? Try erythritol instead to avoid so many empty calories: Erythritol May Be a Sweet Antioxidant.

-Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live year-in-review presentations Uprooting the Leading Causes of Death and More Than an Apple a Day.

Image Credit: Liz West / Flickr

Original Link